1. Vanderbilt University School of Medicine
BRAIN TUMORS
Jeanette Norden, Ph.D.
Professor Emerita
Vanderbilt University School of Medicine

2. CNS TUMORS
CNS tumors (neoplasms): abnormal masses of cells produced by uncontrolled cellular proliferation; can be
Primary: arising from cells in the CNS
Secondary: arising from the spread of cancerous cells from another site in the body
The most common cancers to metastasize to brain are lung, breast, and melanoma
CNS involvement can be the 1st sign of a cancer in the body

3. CNS TUMORS
In the CNS, many different kinds of cells can give rise to primary tumors; more common of these types include:
Meningiomas: arise from meningeal cells; most common primary tumor in CNS
Gliomas: derived from cells that in development arise from glioblasts (immature cells that give rise to “glial” [non-neuronal] cells in the brain)
Ependymomas: arise from ependymal cells that line the ventricles
Oligodendrogliomas: arise from oligodendrocytes; generally slow-growing and benign
Astrocytomas: arise from astrocytes; the most common glial cell tumor in adults
There are a number of genetic risk factors; ↑↑ risk with age and where you live; the only environmental risk factor identified is exposure to ionizing radiation, particularly when young

4. EPENDYMOMAS & GLIOMAS – PRIMARY CNS TUMORS
Oligodendrocytes
Oligodendroglioma
Ependymoma
Astrocytoma

5. CNS TUMORS Brain tumors may be
Benign: non-cancerous; the vast majority (~85%) of meningiomas are benign; slow-growing, non-invasive
Malignant: cancer; fast-growing and invasive
While brain tumor cells rarely metastasize to other parts of the body, they may metastasize within the brain

6. Cancerous tumors are “graded” by their malignancy
CNS TUMORS
Cancerous tumors are “graded” by their malignancy
For example,
Astrocytomas are “graded” from I- IV (low-grade to high-grade); low grade are minimally invasive and slow-growing
High-grade (IV): tumors are rapidly growing, invasive (the cells invade adjacent normal tissue), and “undifferentiated” (cells look immature and in various stages of cell division); Grade IV astrocytomas are also called glioblastoma multiforme (GBMs)
High-grade astrocytomas can arise de novo (primary) or evolve from low-grade astrocytomas (secondary)

7. WHY THERE ARE NO “NEURON” TUMORS IN THE ADULT CNS
In development,
Glioblasts give rise to oligodendrocytes, ependymal cells and astrocytes; all of these cell types are capable of mitosis (cell division to create new cells) throughout life
Neuroblasts give rise to neurons; neurons are post-mitotic cells, meaning that they are not capable of cell division in adults; thus, they do not form tumors in the adult brain
Non-mitotic
Oligodendrocytes
Mitotic

8. CNS TUMORS
CNS TUMORS MAY PRODUCE BOTH GENERALIZED AND LOCALIZED SIGNS/SYMPTOMS
GENERALIZED SYMPTOMS WOULD INCLUDE HEADACHE, SEIZURES, CONFUSION
LOCALIZED SIGNS/SYMPTOMS DEPEND ON WHERE THE TUMOR IS; ADDITIONAL SIGNS/SYMPTOMS WILL BE SEEN AS THE TUMOR GROWS AND EXPANDS TO INVOLVE NEARBY AREAS
IN GENERAL, ONSET OF SIGNS/SYMPTOMS IS PROGRESSIVE

9. In infants and small children, tumors can arise from “immature” cells
Blastoma: neoplasms which are composed of immature, undifferentiated cells
Medulloblastoma: a highly malignant cancer occurring primarily in infants/young children; named because the tumors are composed of immature cells that look like primitive cells of the medullary area of the developing neural tube
Most commonly occur in the vermis (midline area) of the cerebellum – a structure involved in balance, equilibrium, and coordination of learned, skilled motor movement

10. ALL BRAIN TUMORS ARE POTENTIALLY LIFE-THREATENING BECAUSE OF THE POSSIBILITY OF BRAIN HERNIATION
Herniation of the brain can cause death; for example, tonsillar herniation produces pressure on cardiovascular and respiratory centers in the medulla, causing death

11. BRAIN TUMORS
While tumors can occur in the spinal cord, we will confine our discussion to brain tumors – reinforcing that understanding the functional anatomy of the brain is the key to understanding how physicians come to an anatomic diagnosis
Our discussion of Clinical Cases will involve 4 types of tumors:
Medulloblastoma
Meningioma
Glioblastoma multiforme
Astrocytoma

12. CLINICAL CASE I
Cindy is a 28 month old girl, brought to the pediatrician by her Mother who was concerned because the little girl was falling frequently and seemed to have very poor balance. The problems had been present since Cindy had begun to walk (at 13 months), and were getting progressively worse; the child had also become increasingly irritable and withdrawn. The Mother also reported that the child vomited frequently. Upon examination, Cindy was seen to have a broad-based ataxic gait; she required help in sitting, standing, or walking

13. Medulloblastoma Tumor cells in the midline of the cerebellum; causes
Wide-based gait, ataxia, and truncal instability
Nausea and vomiting probably secondary to increased intracranial pressure, as well as pressure on medulla from expanding tumor

14. WHY MEDULLOBLASTOMA IS SO DANGEROUS
It is a malignant cancer
Often not diagnosed early, because infants are “naturally” ataxic (uncoordinated)
Most common site is the midline area of the cerebellum which is close to the 4th ventricle (one of the cavities in the brain that contains Cerebrospinal Fluid [CSF]); malignant cells get into CSF and “seed” to other areas of the brain
4th ventricle can also be blocked by cancer cells – and a hydrocephalus (build-up of CSF in ventricles) can occur which can also cause the brain to herniate

15. WHY MEDULLOBLASTOMA IS SO DANGEROUS
4th Ventricle

16. MENINGIOMA
Most common primary brain tumor (~30% of all brain tumors) in adults
Generally, slow-growing benign (~85%) tumors
Meninges (connective tissue sheaths that surround the brain and spinal cord), from outer to inner
DURA
ARACHNOID
PIA

17. CLINICAL CASE II
A 47 yo Caucasian woman (Mrs. T. D.) goes to her gynecologist for her yearly examination. She tells the gynecologist that over the last year she has been having headaches and depression. No neurological exam was deemed necessary – on the assumption that her headaches and depression were due to perimenopause. Two months later, Mrs. D. was found unconscious by her husband and brought into the Emergency Department by ambulance. He reports that she had been having severe headaches and had been very depressed and difficult to get along with over the last few months.

18. MENINGIOMA MENINGIOMA - compressing the left frontal lobe
Depression was the result of compression of the left frontal lobe; headaches and death were due to increased intracranial pressure and eventual herniation of the brain

19. GLIOBLASTOMA MULTIFORME
Glioblastoma multiforme (GBMs) are highly malignant tumors (Grade IV astrocytomas); they are rapidly growing, invasive, with “undifferentiated” cells

20. CLINICAL CASE III
A 69 yo African-American male professor (Mr. D. M.) at a major medical school has a seizure during a departmental faculty meeting. He is immediately taken to the Emergency Department where an emergent CT shows a mass in his right hemisphere involving the frontal/parietal lobe area/underlying axons. Consultation with neurosurgery indicates that the tumor is inoperable because of how it has invaded surrounding tissue; thus, surgery would require the resection or removal of a large amount of normal tissue. Chemotherapy and radiation were begun in order to shrink the tumor mass and to try and slow the tumor growth.

21. CLINICAL CASE III, Cont. The initial neurological examination revealed
Papilledema (Due to increased intracranial pressure)
Weakness on the left (Involvement of primary motor cortex [Area 4]/underlying axons on the right)
Loss of fine touch, vibration and conscious proprioception on the left (Involvement of primary somatosensory cortex [Areas 3, 1 & 2]/underlying axons on the right)
When asked if he was experiencing headaches he said “yes” and that they were worse in the mornings

22. CLINICAL CASE III, cont. Normal fundus
Appearance of fundus under conditions of increased intracranial pressure (papilledema)

23. CLINICAL CASE III, Cont. Area 4 – primary motor cortex
Areas 3, 1 & 2 – primary somatosensory cortex
Area 4 – primary motor cortex
A tumor is compromising Areas 4 and 3, 1 & 2, and underlying axons
Mr. M. has headaches that are worse in the mornings because of the redistribution of CSF (in the presence of a tumor), when going from a lying down to a standing position

24. CLINICAL CASE III, Cont.
After chemotherapy and radiation, Mr. M. had a few good months. He then developed (in addition to previous signs/symptoms)
Contralateral (left-sided) neglect (Due to growth of the tumor to include posterior parietal cortex/underlying axons on the right)

25. CLINICAL CASE III, Cont. CONTRALATERAL (LEFT) NEGLECT
Posterior Parietal Cortex
Tumor has expanded to now include posterior parietal cortex/underlying axons, causing contralateral (left) neglect of the body & world; also extends to memory

26. CLINICAL CASE III, Cont. CONTRALATERAL NEGLECT
Mr. M has a tumor in the R parietal cortex, causing “neglect” of the L half of the body and world

27. CLINICAL CASE III, Cont. GBMs are highly invasive
Note how the tumor has invaded normal tissue so that it is difficult to tell the difference between normal tissue and the tumor

28. CLINICAL CASE IV Astrocytoma
A 47 yo Caucasian male (Mr. R. W.) goes to his Primary Care Physician for his yearly “wellness” visit. During the neuro portion of his physical examination, the physician notes that Mr. W. has lost his sense of smell, and that he has a “grasp” reflex.
After being referred to a Neurologist, a CT is done and a large tumor is identified in the anterior cranial fossa.

29. CLINICAL CASE IV, Cont. CT WITH CONTRAST
(Tumors lack a blood-brain barrier which is why this tumor is showing up bright “white” when a contrast agent is given)

30. CLINICAL CASE IV, Cont.
The tumor is at the base of the brain, anteriorly
The tumor crosses the midline and has affected both frontal lobes and olfactory structures
FRONTAL LOBE
FRONTAL
LOBE
The brain is “upside down” so that the ventral underside of the brain is visible; the blue circle indicates the extent of the tumor
OLFACTORY BULBS

31. CLINICAL CASE IV, Cont.
The loss of smell (anosmia) is because the olfactory bulbs have been affected bilaterally
The “grasp” reflex is a reflex seen normally in infants; it is inhibited by the frontal lobe during development; thus, the re-appearance of the reflex in an adult is a pathological sign; it signals compromise of the prefrontal cortex

32. CLINICAL CASE IV, Cont.
Mr. W. had surgery to remove the tumor; he has done well. He does show persistent anosmia (they were unable to save the olfactory bulbs) and difficulty “inhibiting” his behavior. The latter is due to damage to the prefrontal cortex which occurred both because of the tumor and its removal.
Post-surgical MRI; area where the tumor was removed is filled with CSF

33. TAKE-HOME MESSAGES
If you or a loved one experience progressive headache, confusion, memory loss, loss of function (motor, sensory, etc.), or other events (like a seizure), notify your Primary Care Physician!
If a brain tumor is identified, survival depends on many factors – but early diagnosis is important if surgery is an option
Also remember: CNS involvement could be the 1st sign of a cancer in the body – again early detection is important!